N-(2-ethyl chloride)-N-nitrosoureas ("CNU"), such as 1,3-bis-(2-ethyl chloride)-1-nitrosourea (BCNU), 1-(2-ethyl chloride)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-ethyl chloride)3-(4-methyl) cyclohexyl-1-nitrosourea (MeCCNU) are important antineoplastic chemotherapeutic agents, from the clinical standpoint as well. (Nitroso-ureas in Cancer treatment, B. Serrou, P. S. Schein and J.-L. Imbach, editors, Elsevier/North-Holland Biomedicals Press, 1981; Nitrosoureas: current status and new developments, Academic Press, New York, 1981).
Along with their therapeutic efficacy, however, these substances also have a long-lasting cumulative toxicity (Eisenbrand et al., in: Nitrosoureas in Cancer Treatment, Elsevier 1981).
In order to obtain substances having a better therapeutic index, nitrosoureas have lately been synthesized with various substitutions (for instance, sugar, peptides, DNA bases) and experimentally tested.
It has been found that a series of tumors contain hormone receptors or are hormone-dependent. The attempt has already been made several times to improve the chemotherapy of such tumors by chemically bonding alkylanes, for example, to hormones in order to exploit the receptor affinity of the hormones for attaining target-specific transporting of the cytostatic alkylane into the tumor tissue. Some examples of substances of this type are Prednimustin.RTM., an ester of prednisolone and the alkylane chlorambucil (a phenyl-butyric acid-mechlorethamine hydrochloride derivative), or Estracyt.RTM., an N,N-bis (2-ethyl chloride)-3-carbamate of the estradiol-17-.beta.-phosphate. (Cancer Chemotherapy, edited by H. M. Pinedo, Excerpta Medica, Amsterdam-Oxford, 1979 and 1980.)